Genetic Variant ZNF474:p.Ile27Asn (chr5-122152070-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207317.3(ZNF474):c.80T>A(p.Ile27Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

ZNF474
NM_207317.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Publications

3 publications found

Variant links:

Genes affected

ZNF474 (HGNC:23245): (zinc finger protein 474) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF474 links:

ZNF475 (HGNC:53564): (zinc finger protein 475)

ZNF475 links:

ENSG00000247311 (HGNC:):

ENSG00000247311 links:

ZNF474-AS1 (HGNC:41019): (ZNF474 antisense RNA 1)

ZNF474-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019510716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207317.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF474	NM_207317.3	MANE Select	c.80T>A	p.Ile27Asn	missense	Exon 2 of 2	NP_997200.1	Q6S9Z5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF474	ENST00000296600.5	TSL:1 MANE Select	c.80T>A	p.Ile27Asn	missense	Exon 2 of 2	ENSP00000296600.4	Q6S9Z5
ZNF474	ENST00000698749.1		c.80T>A	p.Ile27Asn	missense	Exon 2 of 4	ENSP00000513911.1	A0A8V8TNM7
ZNF474	ENST00000698748.1		c.80T>A	p.Ile27Asn	missense	Exon 2 of 6	ENSP00000513910.1	A0A8V8TM77

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000724

AC:

182

AN:

251302

AF XY:

0.000810

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00139

AC:

2032

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33480

American (AMR)

AF:

0.000246

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00108

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00166

AC:

1849

AN:

1111996

Other (OTH)

AF:

0.00103

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

132

265

397

530

662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152332

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41578

American (AMR)

AF:

0.000458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00168

AC:

114

AN:

68022

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000869

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.000782

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0056

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.049

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.67

M_CAP

Benign

0.036

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.3

PhyloP100

2.5

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.48

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

0.0010

Vest4

0.63

MVP

0.12

MPC

0.0082

ClinPred

0.050

GERP RS

3.7

Varity_R

0.32

gMVP

0.041

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over